Retinal pigment epithelium (RPE), a single layer of cells present between the retina and choroid in the eye, is vital for the normal functioning of the retina. Many of the inflammatory, infectious and hereditary diseases of the retina are associated with the degeneration and /or dysfunction of the RPE. We have developed human RPE cell culture system and have used this as a model to investigate the various roles of RPE in the pathophysiology of retinal disorders. We have focussed our attention on Transforming Growth factor-beta (TGF-b), since TGF-b is involved in retinal disorders of proliferative, inflammatory and infectious etiology. Retinal and Choroidal neovascularization (NV), observed during age related macular degeneration (ARMD) and diabetic retinopathy, are the leading causes of visual impairment. Elevated expression of TGF-b in vitreous, retina and RPE has been closely correlated with the retinal fibrosis and choroidal neovascularization. Since vascular endothelial growth factor (VEGF) is associated with NV, we have examined the role of RPE in VEGF expression. TGF-b is found to be the potent inducer of VEGF secretion by RPE. Effects of TGF-b are specific since other related growth factors had no effects, and TGF-b effects are neutralized by TGF-b receptor II antibody. RT-PCR analyses indicated the expression of 121,165 and 189 aa isoforms of VEGF mRNA, which are up regulated by TGF-b. By using specific inhibitors of mitogen activated protein kinases and Northern blot analyses, we found that TGF-b activate VEGF transcription through MAPK and smad pathways. Regulation of the expression of VEGF in RPE by TGF-b strongly suggests an important role for TGF-b in neovascularization associated with retinal disorders.